Effects of divalent metal ions on the alpha beta-crystallin chaperone-like activity: spectroscopic evidence for a complex between copper(II) and protein

aB-crystallin is a small heat shock protein, showing chaperone-like activity, that is expressed in the lens and in several other
tissues. The role of some metal ions in the aB-crystallin biology starts to be well documented. In some neuro-degenerative pathologies,
like Parkinson and Alzheimer’s diseases, aB-crystallin is expressed at high levels. In the same pathologies an accumulation
of divalent metal cations is observed. In order to investigate the interactions between human aB-crystallin and divalent metal ions,
the effect of copper, zinc and calcium on the chaperone-like activity of the protein has been studied. Copper and zinc at concentrations
0.1 and 1 mM significantly increase the chaperone-like activity, whereas calcium 1 mM completely inhibits activity. Electron
paramagnetic resonance (EPR) and circular dichroism (CD) spectra indicate the possible complex formation between Cu(II) and
protein at physiological pH. Molecular modeling calculations, carried out for the probable Cu(II) binding site, suggest that a
complex with three histidine residues is possible.